As a synthetic method of a quinoline derivative, for example, (E)-3-(4′-(4″-fluorophenyl)-2′-cyclopropylquinolin-3′-YL)PROPENE aldehyde, there are known (1) a method comprising reacting cis-1-ethoxy-2-(tri-n-butylstannyl)ethylene with butyllithium in tetrahydrofuran, reacting the resulting compound with 4-(4′-fluorophenyl)-2-cyclopropylquinoline-3-carbaldehyde at −60 to −78° C., and hydrolyzing the obtained vinyl ether compound in the presence of an acid catalyst; and (2) a method comprising reacting 4-(4′-fluorophenyl)-2-cyclopropylquinoline-3-carbaldehyde with alkoxycarbonylmethyl phosphonate to give the corresponding α, β-unsaturated carboxylic acid ester, reducing an ester moiety of this compound with, for example, a metal hydride such as diisobutyl aluminum hydride and the like to give an alcohol, and oxidizing the alcohol with an oxidant such as activated manganese dioxide and the like (see JP-A-1-279866, EP-A-304063, U.S. Pat. No. 5,856,336).
As regards the above-mentioned method (1), the organotin compound to be used is industrially difficult to obtain, and needs to be reacted at an extremely low temperature of −60 to −78° C., thus requiring special reaction equipment. As regards the above-mentioned method (2), the metal hydride to be used for reducing the ester moiety is difficult to handle. In addition, plural steps are necessary until the objective product is obtained by either method, which makes these methods not entirely advantageous as an industrial production method of a quinoline derivative such as (E)-3-(4′-(4″-fluorophenyl)-2′-cyclopropylquinolin-3′-yl)propene aldehyde.
As a synthetic method of quinolinecarbaldehyde, such as 4-(4′-fluorophenyl)-2-cyclopropylquinoline-3-carbaldehyde, which is an intermediate for the above-mentioned quinoline derivative, there are known (3) a method comprising reducing the corresponding quinoline carboxylic acid ester with various metal hydrides, such as diisobutylaluminum hydride and the like, to give the corresponding quinoline carbinol (4-(4′-FLUOROPHENYL)-2-cyclopropyl-3-hydroxymethylquinoline), then oxidizing this compound with pyridinium chlorochromate, oxalyl chloride/dimethyl sulfoxide/tertiary amine (Swern oxidation), or sulfur trioxide pyridine complex and the like (see JP-A-1-279866, EP-A-304063, U.S. Pat. No. 5,856,336); and (4) a method comprising oxidizing 4-(4′-fluorophenyl)-2-cyclopropyl-3-hydroxymethylquinoline with a hypohalous acid salt in the presence of a nitroxy radical derivative (see JP-A-8-27114).
The above-mentioned (3) and (4) comprise oxidation of an alcohol moiety into aldehyde using the corresponding quinoline carbinol as a starting material for the production of quinolinecarbaldehyde, which requires complicated steps because quinoline carbinol needs to be obtained by reducing the corresponding quinoline carboxylic acid ester. In addition, pyridinium chlorochromate used as an oxidant in method (3) is associated with a problem of treatment of a waste liquid containing an environmentally harmful chromium ion, and byproduction of dimethyl sulfide that generates extreme odor under Swern oxidation conditions and conditions using a sulfur trioxide pyridine complex. For the oxidation reaction using a hypohalous acid salt, moreover, an environmentally harmful halogenated hydrocarbon, such as dichloromethane and the like, needs to be generally used as a solvent. Therefore, the above-mentioned methods are hardly considered an industrial production method of quinolinecarbaldehyde.
It is therefore an object of the present invention to provide a method capable of producing a quinoline derivative and an intermediate thereof efficiently and industrially advantageously by shorter steps, using chemicals that are industrially easily obtainable and easily handled.